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The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation
The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation
Background: Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease modifying anti-rheumatic drugs (DMARD) such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.

Objective: To assess the clinical and cost-effectiveness of four biologic DMARDs (etanercept, abatacept, adalimumab and tocilizumab - with or without methotrexate where indicated) for the treatment of JIA (systemic or oligoarticular JIA excluded).

Data sources: Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and DARE were searched for published studies from inception to May 2015 for English language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.

Review methods: Systematic reviews of clinical-effectiveness, health-related quality of life and cost-effectiveness were undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision analytic model was developed to compare estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base case time horizon was 30 years and the model took a National Health Service (NHS) perspective, with costs and benefits discounted at 3.5%.

Results: Four placebo-controlled RCTs met the inclusion criteria for the clinical-effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi) 30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar with fewer disease flares and greater proportions with ACR Pedi 50 and 70 responses among participants randomised to continued biologic DMARD. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that generally ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality of life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratio (ICER) for adalimumab, etanercept and tocilizumab versus methotrexate was £38,127, £32,526 and £38,656 per QALY, respectively. The ICER for abatacept versus methotrexate as a second line biologic was £39,536 per QALY.

Limitations: The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs and clinical evidence for specific JIA subtypes is limited.

Conclusions: Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA, and an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow- are needed to establish comparative effectiveness. RCTs for JIA subtypes where evidence is lacking are also required.

Funding: The National Institute for Health Research Health Technology Assessment programme.
1366-5278
Shepherd, Jonathan
dfbca97a-9307-4eee-bdf7-e27bcb02bc67
Cooper, Keith
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Harris, Petra
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Picot, Jo
324d6f20-a105-49fd-9fb0-88791be84ada
Rose, Micah
f6deee44-f21f-4d14-90a9-f7a449d0adba
Shepherd, Jonathan
dfbca97a-9307-4eee-bdf7-e27bcb02bc67
Cooper, Keith
ea064f58-d71d-404a-bcf3-49d243b8825b
Harris, Petra
a8bd143b-3e2c-4929-9279-510a4c60bd09
Picot, Jo
324d6f20-a105-49fd-9fb0-88791be84ada
Rose, Micah
f6deee44-f21f-4d14-90a9-f7a449d0adba

Shepherd, Jonathan, Cooper, Keith, Harris, Petra, Picot, Jo and Rose, Micah (2016) The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation. Health Technology Assessment, 20 (34). (doi:10.3310/hta20340). (PMID:27135404)

Record type: Article

Abstract

Background: Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease modifying anti-rheumatic drugs (DMARD) such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.

Objective: To assess the clinical and cost-effectiveness of four biologic DMARDs (etanercept, abatacept, adalimumab and tocilizumab - with or without methotrexate where indicated) for the treatment of JIA (systemic or oligoarticular JIA excluded).

Data sources: Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and DARE were searched for published studies from inception to May 2015 for English language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.

Review methods: Systematic reviews of clinical-effectiveness, health-related quality of life and cost-effectiveness were undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision analytic model was developed to compare estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base case time horizon was 30 years and the model took a National Health Service (NHS) perspective, with costs and benefits discounted at 3.5%.

Results: Four placebo-controlled RCTs met the inclusion criteria for the clinical-effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi) 30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar with fewer disease flares and greater proportions with ACR Pedi 50 and 70 responses among participants randomised to continued biologic DMARD. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that generally ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality of life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratio (ICER) for adalimumab, etanercept and tocilizumab versus methotrexate was £38,127, £32,526 and £38,656 per QALY, respectively. The ICER for abatacept versus methotrexate as a second line biologic was £39,536 per QALY.

Limitations: The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs and clinical evidence for specific JIA subtypes is limited.

Conclusions: Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA, and an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow- are needed to establish comparative effectiveness. RCTs for JIA subtypes where evidence is lacking are also required.

Funding: The National Institute for Health Research Health Technology Assessment programme.

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Accepted/In Press date: 31 March 2016
e-pub ahead of print date: 1 April 2016
Published date: 1 May 2016
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 394343
URI: http://eprints.soton.ac.uk/id/eprint/394343
ISSN: 1366-5278
PURE UUID: f4bea991-cc2a-4728-8428-3529b790a6e4
ORCID for Jonathan Shepherd: ORCID iD orcid.org/0000-0003-1682-4330
ORCID for Petra Harris: ORCID iD orcid.org/0000-0001-9257-3786
ORCID for Jo Picot: ORCID iD orcid.org/0000-0001-5987-996X

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Date deposited: 18 May 2016 09:36
Last modified: 18 Feb 2021 17:02

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Author: Keith Cooper
Author: Petra Harris ORCID iD
Author: Jo Picot ORCID iD
Author: Micah Rose

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